Transcriptomic landscape of Pituitary Adenomas: potential diagnostic and therapeutic targets

Abstract Objective Pituitary adenomas (PAs) account for 10–15% of intracranial neoplasms. Although generally benign, many PAs, especially non-functional types lack effective medical treatments. Cell membrane proteins are promising targets for diagnosis and therapy due to their accessibility and specificity. This study aimed to identify shared and subtype-specific deregulated membrane proteins across PA types and evaluate the potential of natural compounds and small molecules to inhibit these targets. Methods Eight microarray datasets comprising 77 PA and 25 normal pituitary samples were analyzed using the Limma package in R version 4.3.0. Batch effects were removed with ComBat. Differentially expressed genes (DEGs) were identified and filtered for membrane proteins. Functional annotation was performed using EnrichR. Structures of key proteins were retrieved from PDB/AlphaFold and docked with plant-derived compounds and small molecules using PyRx. Results FILIP1L (upregulated) and ISRL (downregulated) were identified as shared membrane protein targets across all PA subtypes. Subtype-specific upregulated membrane proteins included THY1 (GH), ADD1 and TSPAN6 (PRL), and CX3CR1, FOLR1, and RAMP1 (NFPA). Docking analysis highlighted strong binding affinities between several natural compounds and proteins FOLR1, GRIK1, and TLN1. The FDA-approved drug Mirvetuximab soravtansine also showed potential in targeting FOLR1. Conclusion Subtype-specific and shared membrane proteins in PAs represent viable diagnostic and therapeutic targets. Natural compounds and repurposed drugs may offer new treatment strategies, particularly for non-functional and invasive PAs.